Development of a triclosan scaffold which allows for adaptations on both the A- and B-ring for transport peptides

The enoyl acyl-carrier protein reductase (ENR) enzyme is harbored within the apicoplast of apicomplexan parasites providing a significant challenge for drug delivery, which may be overcome through the addition of transductive peptides, which facilitates crossing the apicoplast membranes. The binding...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2013-06, Vol.23 (12), p.3551-3555
Main Authors: Muench, Stephen P., Stec, Jozef, Zhou, Ying, Afanador, Gustavo A., McPhillie, Martin J., Hickman, Mark R., Lee, Patty J., Leed, Susan E., Auschwitz, Jennifer M., Prigge, Sean T., Rice, David W., McLeod, Rima
Format: Article
Language:English
Subjects:
Apicomplexa
Binding Sites
Carrier Proteins - chemistry
Carrier Proteins - metabolism
drugs
Enoyl reductase
Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) - antagonists & inhibitors
Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) - chemistry
Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) - metabolism
Models, Molecular
parasites
peptides
Plasmodium
Plasmodium falciparum - metabolism
solvents
Toxoplasma
Toxoplasma - metabolism
transporters
Triclosan
Triclosan - analogs & derivatives
Triclosan - chemical synthesis
Triclosan - chemistry
Triclosan - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The enoyl acyl-carrier protein reductase (ENR) enzyme is harbored within the apicoplast of apicomplexan parasites providing a significant challenge for drug delivery, which may be overcome through the addition of transductive peptides, which facilitates crossing the apicoplast membranes. The binding site of triclosan, a potent ENR inhibitor, is occluded from the solvent making the attachment of these linkers challenging. Herein, we have produced 3 new triclosan analogs with bulky A- and B-ring motifs, which protrude into the solvent allowing for the future attachment of molecular transporters for delivery.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2013.04.035